tbuckley/cabot-search huggingface dataset:
CCL2 chemokine inhibition primes the tumor vasculature for improved nanomedicine delivery and efficacy
Authors: Diana Möckel, Matthias Bartneck, Patricia Niemietz, Maike Wagner, Josef Ehling, Elena Rama, Marek Weiler, Felix Gremse, Dirk Eulberg, Robert Pola, Michal Pechar, Tomas Etrych, Gert Storm, Fabian Kiessling, Frank Tacke, Twan Lammers
Journal: Journal of Controlled Release (2023)
A radioactive CRISPR interference system using 89Zr-labeled LbCas12a
Authors: Injoo Hwang, Jun Young Lee, Tae-Hyun Kim, Eun Ju Lee, Jeeho Kim, Hyomin Park, Min Goo Hur, Sanghwa Lee, Jeong-Hoon Park
Journal: Journal of Controlled Release (2023)

Recently, CRISPR proteins have been recognized as promising candidates for drug development. However, there is still a lack of substances with the appropriate sensitivity and stability for targeted drug delivery systems. 89Zr is a radioactive isotope that emits positrons, allowing real-time in vivo tracking with proven safety. In this study, we confirmed that labeling with 89Zr did not compromise the functionality of CRISPR proteins during in vivo behavioral imaging. Furthermore, we demonstrated the therapeutic efficacy of the CRISPR interference system in a mouse model of liver fibrosis, highlighting the theragnostic potential of isotope-labeled CRISPR proteins. The findings of this research could contribute to various aspects of ongoing clinical studies exploring the in vivo applications of CRISPR proteins.
Safety and effectiveness of totally laparoscopic total gastrectomy vs laparoscopic-assisted total gastrectomy: a meta-analysis
Authors: Qishuan Wu, Yan Wang, Qifan Peng, Mingshuai Bai, Zhou Shang, Leping Li, Feng Tian, Changqing Jing
Journal: International Journal of Surgery (2023)

Background: For gastric cancer with total gastrectomy, the usual laparoscopic surgical approaches are totally laparoscopic total gastrectomy (TLTG) and laparoscopic-assisted total gastrectomy (LATG). Due to its difficult anastomotic technique, the adoption of TLTG is limited. Therefore, surgeons prefer using LATG, which also led to TLTG being somewhat overlooked, so there is no clear conclusion today as to which surgical procedure is more favorable to the patient’s recovery. This article aimed to compare the safety and short-term outcomes of the two surgical approaches. Materials and methods: Studies comparing TLTG and LATG, published up to December 2022, were searched in PubMed, Web of Science, and Embase databases. The study outcomes, including operative time, blood loss, anastomosis time, number of retrieved lymph nodes, proximal and distal resection margins, time to first fluid and soft diet, hospitalization duration, time to first flatus, and postsurgical and anastomotic complications, were compared between these two different surgical procedures. Statistics were analyzed with RevMan 5.4 and Stata 13.1. Results: Fifteen publications were included in this study. The total sample included 3023 cases. The meta-analysis revealed no significant difference in overall postoperative complications between the two surgical approaches ( P &gt;0.05). Compared with LATG, TLTG led to reduced intraoperative blood loss ( P &lt;0.0001), an increased number of lymphatic node dissections ( P &lt;0.0001), and decreased hospitalization duration ( P =0.002). However, operative time, anastomosis time, pulmonary infection, resection margins, time to first fluid and soft diet, time to first flatus and anastomosis-related complications were no significant difference between TLTG and LATG groups ( P &gt;0.05). Conclusion: TLTG did not lead to an increase in overall postoperative complications, which is a reliable surgical approach for treatment of gastric cancer. Moreover, it may reduce harm to patients and enable them to obtain better surgical outcomes.
Approaches and challenges to inferring the geographical source of infectious disease outbreaks using genomic data
Authors: Zhiyuan Chen, Philippe Lemey, Hongjie Yu
Journal: The Lancet Microbe (2023)

Genomic data hold increasing potential in the elucidation of transmission dynamics and geographical sources of infectious disease outbreaks. Phylogeographic methods that use epidemiological and genomic data obtained from surveillance enable us to infer the history of spatial transmission that is naturally embedded in the topology of phylogenetic trees as a record of the dispersal of infectious agents between geographical locations. In this Review, we provide an overview of phylogeographic approaches widely used for reconstructing the geographical sources of outbreaks of interest. These approaches can be classified into ancestral trait or state reconstruction and structured population models, with structured population models including popular structured coalescent and birth-death models. We also describe the major challenges associated with sequencing technologies, surveillance strategies, data sharing, and analysis frameworks that became apparent during the generation of large-scale genomic data in recent years, extending beyond inference approaches. Finally, we highlight the role of genomic data in geographical source inference and clarify how this enhances understanding and molecular investigations of outbreak sources.
The Role of Abdominal CT in the Management of Acute Abdominal Conditions in Children
Authors: Osnat Zmora, Atara Indursky, Gal Becker, Netanel Agajany, Osnat Zmora, Rachel Aber, Vasilina Kaminsky
Journal: International Journal of Surgery (2023)

Objectives: This study aimed to assess the influence of abdominal computerized tomography (CT) scans on the management of children presenting with acute abdominal conditions, considering concerns regarding radiation exposure. Methods: A retrospective review was conducted of all acute pediatric patients who underwent abdominal CT in a tertiary hospital, during 2018-2019. Results: Over the 2-year period, 976 pediatric patients were admitted due to acute abdominal conditions. Of 197 (20.2%) patients who underwent abdominal CT scans, management plan was modified based on CT results in 67.5%. In non-trauma cases, the impact on the management plan was even more pronounced, affecting 91.2% of patients, and led to invasive procedures (one third), non-invasive actions (one third), or discharge (one third). Multivariate analysis demonstrated a significantly higher odds ratios (OR) for impact on management in non-trauma patients (OR=24) as compared to trauma patients, especially younger (OR=1.58 annually) and male (OR=10.42) patients, and when performed early (OR=2.44, for each day earlier). Trauma patients with a lower body mass index (BMI) (OR=1.02 per percentile decrease) demonstrated a significantly larger impact. Conclusion: These results support a more liberal use of early CT scans in non-traumatic acute pediatric abdominal conditions, especially in younger male patients, with more careful consideration in trauma patients, particularly those with high BMIs.
Gene interaction network analysis in multiple myeloma detects complex immune dysregulation associated with shorter survival
Authors: Anish K. Simhal, Kylee H. Maclachlan, Rena Elkin, Jiening Zhu, Larry Norton, Joseph O. Deasy, Jung Hun Oh, Saad Z. Usmani, Allen Tannenbaum
Journal: Blood Cancer Journal (2023)

Abstract The plasma cell cancer multiple myeloma (MM) varies significantly in genomic characteristics, response to therapy, and long-term prognosis. To investigate global interactions in MM, we combined a known protein interaction network with a large clinically annotated MM dataset. We hypothesized that an unbiased network analysis method based on large-scale similarities in gene expression, copy number aberration, and protein interactions may provide novel biological insights. Applying a novel measure of network robustness, Ollivier-Ricci Curvature, we examined patterns in the RNA-Seq gene expression and CNA data and how they relate to clinical outcomes. Hierarchical clustering using ORC differentiated high-risk subtypes with low progression free survival. Differential gene expression analysis defined 118 genes with significantly aberrant expression. These genes, while not previously associated with MM, were associated with DNA repair, apoptosis, and the immune system. Univariate analysis identified 8/118 to be prognostic genes; all associated with the immune system. A network topology analysis identified both hub and bridge genes which connect known genes of biological significance of MM. Taken together, gene interaction network analysis in MM uses a novel method of global assessment to demonstrate complex immune dysregulation associated with shorter survival.
Immunosignatures associated with TP53 status and co-mutations classify prognostically head and neck cancer patients
Authors: Andrea Sacconi, Paola Muti, Claudio Pulito, Giulia Urbani, Matteo Allegretti, Raul Pellini, Nikolay Mehterov, Uri Ben-David, Sabrina Strano, Paolo Bossi, Giovanni Blandino
Journal: Molecular Cancer (2023)

Immune checkpoint inhibitors (ICIs) are a therapeutic strategy for various cancers although only a subset of patients respond to the therapy. Identifying patients more prone to respond to ICIs may increase the therapeutic benefit and allow studying new approaches for resistant patients.
Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study
Authors: Kathrine Dyhr Lycke, Johnny Kahlert, Lone Kjeld Petersen, Rikke Kamp Damgaard, Li C Cheung, Patti E Gravitt, Anne Hammer
Journal: BMJ (2023)

To describe the long term risk of cervical cancer in women with untreated (that is, undergoing active surveillance) or immediately treated cervical intraepithelial neoplasia grade 2 (CIN2).Nationwide population based historical cohort study.Danish healthcare registries.Women with CIN2 diagnosed in 1998-2020 and aged 18-40 years at diagnosis, who had either active surveillance or immediate treatment with large loop excision of the transformation zone (LLETZ). Women with a previous record of CIN2 or worse or LLETZ were excluded.A Weibull survival model for interval censored time-to-event data was used to estimate the cumulative risk of cervical cancer. Inverse probability treatment weighting was used to adjust estimates for age, index cytology, calendar year, and region of residence.The cohort included 27 524 women with CIN2, of whom 12 483 (45%) had active surveillance and 15 041 (55%) had immediate LLETZ. During follow-up, 104 cases of cervical cancer were identified-56 (54%) in the active surveillance group and 48 (46%) in the LLETZ group. The cumulative risk of cervical cancer was comparable across the two groups during the active surveillance period of two years. Thereafter, the risk increased in the active surveillance group, reaching 2.65% (95% confidence interval 2.07% to 3.23%) after 20 years, whereas it remained stable in the LLETZ group at 0.76% (0.58% to 0.95%).Undergoing active surveillance for CIN2, thereby leaving the lesion untreated, was associated with increased long term risk of cervical cancer compared with immediate LLETZ. These findings show the importance of continued follow-up of women having active surveillance.
Air pollution deaths attributable to fossil fuels: observational and modelling study
Authors: Jos Lelieveld, Andy Haines, Richard Burnett, Cathryn Tonne, Klaus Klingmüller, Thomas Münzel, Andrea Pozzer
Journal: BMJ (2023)

Abstract Objectives To estimate all cause and cause specific deaths that are attributable to fossil fuel related air pollution and to assess potential health benefits from policies that replace fossil fuels with clean, renewable energy sources. Design Observational and modelling study. Methods An updated atmospheric composition model, a newly developed relative risk model, and satellite based data were used to determine exposure to ambient air pollution, estimate all cause and disease specific mortality, and attribute them to emission categories. Data sources Data from the global burden of disease 2019 study, observational fine particulate matter and population data from National Aeronautics and Space Administration (NASA) satellites, and atmospheric chemistry, aerosol, and relative risk modelling for 2019. Results Globally, all cause excess deaths due to fine particulate and ozone air pollution are estimated at 8.34 million (95% confidence interval 5.63 to 11.19) deaths per year. Most (52%) of the mortality burden is related to cardiometabolic conditions, particularly ischaemic heart disease (30%). Stroke and chronic obstructive pulmonary disease both account for 16% of mortality burden. About 20% of all cause mortality is undefined, with arterial hypertension and neurodegenerative diseases possibly implicated. An estimated 5.13 million (3.63 to 6.32) excess deaths per year globally are attributable to ambient air pollution from fossil fuel use and therefore could potentially be avoided by phasing out fossil fuels. This figure corresponds to 82% of the maximum number of air pollution deaths that could be averted by controlling all anthropogenic emissions. Smaller reductions, rather than a complete phase-out, indicate that the responses are not strongly non-linear. Reductions in emission related to fossil fuels at all levels of air pollution can decrease the number of attributable deaths substantially. Estimates of avoidable excess deaths are markedly higher in this study than most previous studies for these reasons: the new relative risk model has implications for high income (largely fossil fuel intensive) countries and for low and middle income countries where the use of fossil fuels is increasing; this study accounts for all cause mortality in addition to disease specific mortality; and the large reduction in air pollution from a fossil fuel phase-out can greatly reduce exposure. Conclusions Phasing out fossil fuels is deemed to be an effective intervention to improve health and save lives as part the United Nations' goal of climate neutrality by 2050. Ambient air pollution would no longer be a leading, environmental health risk factor if the use of fossil fuels were superseded by equitable access to clean sources of renewable energy.
Phasing out fossil fuels would save millions of lives worldwide
Authors: Heli Lehtomäki, Shilpa Rao, Otto Hänninen
Journal: BMJ (2023)

Background High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years.However, neither national nor provincial level burden of disease attributable to multiple IAPs has been reported for China.This is the first study to estimate and rank the annual burden of disease and the financial costs attributable to targeted residential IAPs at the national and provincial level in China from 2000 to 2017.Methods We first did a systematic review and meta-analysis of 117 articles from 37 231 articles identified in major databases, and obtained exposure-response relationships for the candidate IAPs.The exposure levels to these IAPs were then collected by another systematic review of 1864 articles selected from 52 351 articles.After the systematic review, ten IAPs with significant and robust exposure-response relationships and sufficient exposure data were finally targeted: PM 2•5 , nitrogen dioxide, sulphur dioxide, ozone, carbon monoxide, radon, formaldehyde, benzene, toluene, and p-dichlorobenzene.The annual exposure levels in residences were then evaluated in all 31 provinces in mainland China continuously from 2000 to 2017, using the spatiotemporal Gaussian process regression model to analyse indoor originating IAPs, and the infiltration factor method to analyse outdoor originating IAPs.The disabilityadjusted life-years (DALYs) attributable to the targeted IAPs were estimated at both national and provincial levels in China, using the population attributable fraction method.Financial costs were estimated by an adapted human capital approach.Findings From 2000 to 2017, annual DALYs attributable to the ten IAPs in mainland China decreased from 4620 (95% CI 4070-5040) to 3700 (3210-4090) per 100 000.Nevertheless, in 2017, IAPs still ranked third among all risk factors, and their DALYs and financial costs accounted for 14•1% (95% CI 12•3-15•6) of total DALYs and 3•45% (3•01-3•82) of the gross domestic product.Specifically, the rank of ten targeted IAPs in order of their contribution to DALYs in 2017 was PM 2•5 , carbon monoxide, radon, benzene, nitrogen dioxide, ozone, sulphur dioxide, formaldehyde, toluene, and p-dichlorobenzene.The DALYs attributable to IAPs were 9•50% higher than those attributable to outdoor air pollution in 2017.For the leading IAP, PM 2•5 , the DALYs attributable to indoor origins are 18•3% higher than those of outdoor origins.Interpretation DALYs attributed to IAPs in China have decreased by 20•0% over the past two decades.Even so, they are still much higher than those in the USA and European countries.This study can provide a basis for determining which IAPs to target in various indoor air quality standards and for estimating the health and economic benefits of various indoor air quality control approaches, which will help to reduce the adverse health effects of IAPs in China.
Magnet-assisted traction method helps to reduce the difficulty of esophageal endoscopic submucosal dissection
Authors: Yuan Gao, Wei Liu, Liansong Ye, Jiang Du, Jia Xie, Qiongying Zhang, Bing Hu
Journal: Endoscopy (2023)

Endoscopic submucosal dissection (ESD) is the main treatment of early esophageal cancers and precancerous lesions. However, esophageal ESD is extremely demanding technically because sometimes exposure of the submucosal layer is challenging, which increases the difficulty of the operation and the risk of perforation [1] [2]. In this study, we used a magnet-assisted traction method to reduce the difficulty and increase the safety of esophageal ESD.
A Superlong‐Acting Growth Hormone‐Polypeptide Fusion for Growth Hormone Deficiency Treatment
Authors: Zhaoying Yang, Qiongqiong Yao, Like Gong, Fan Zhang, Jiawei Sun, Yuanzi Sun, Weiping Gao
Journal: Advanced Healthcare Materials (2023)

Recombinant human growth hormone (rhGH) is clinically used to treat growth hormone deficiency (GHD). However, daily administration of rhGH is required due to its poor stability and short blood circulation, which causes pains and burdens as well as inconvenience to patients. In this study, a method for genetically fusing rhGH to a thermosensitive polymer of elastin-like polypeptide (ELP) is reported, using which the rhGH-ELP thermosensitive fusion protein can be purified by the thermosensitivity of ELP instead of chromatography. The ELP fusion not only drastically improves the stability of rhGH, but also enables the in situ formation of a sustained-release depot of rhGH-ELP upon subcutaneous (SC) injection, which exhibits gentle release with a platform-to-trough fluctuation in blood and a very long circulatory half-life of 594.6 h. In contrast, rhGH exhibits a peak-to-trough fluctuation in blood with a very short circulatory half-life of 0.7 h. As a result, a single subcutaneous injection of rhGH-ELP can consecutively promote the linear growth of rats and the development of major tissues and organs over 3 weeks without obvious side effects, whereas rhGH is required to be injected daily to achieve similar therapeutic results.
Enhancing Bone Regeneration through CDC20‐Loaded ZIF‐8 Nanoparticles Wrapped in Erythrocyte Membranes with Targeting Aptamer
Authors: Yangge Du, Tian Deng, Yihong Cheng, Qin Zhao, Haibin Xia, Yaoting Ji, Yufeng Zhang, Qing He
Journal: Advanced Healthcare Materials (2023)

Abstract In the context of bone regeneration, nanoparticles harboring osteogenic factors have emerged as pivotal agents for modulating the differentiation fate of stem cells. However, persistent challenges surrounding biocompatibility, loading efficiency, and precise targeting ability warrant innovative solution. In this study, a novel nanoparticle platform founded upon the zeolitic imidazolate framework‐8 (ZIF‐8) is introduced. This new design, CDC20@ZIF‐8@eM‐Apt, involves the envelopment of ZIF‐8 within an erythrocyte membrane (eM) cloak, and is coupled with a targeting aptamer. ZIF‐8, distinguished by its porosity, biocompatibility, and robust cargo transport capabilities, constitutes the core framework. Cell division cycle protein 20 homolog (CDC20) is illuminated as a new target in bone regeneration. The eM plays a dual role in maintaining nanoparticle stability and facilitating fusion with target cell membranes, while the aptamer orchestrates the specific recruitment of bone marrow mesenchymal stem cells (BMSCs) within bone defect sites. Significantly, CDC20@ZIF‐8@eM‐Apt amplifies osteogenic differentiation of BMSCs via the inhibition of NF‐κB p65, and concurrently catalyzes bone regeneration in two bone defect models. Consequently, CDC20@ZIF‐8@eM‐Apt introduces a pioneering strategy for tackling bone defects and associated maladies, opening novel avenues in therapeutic intervention.
Corrigendum to “Comparison of HAV and HCV infections in vivo and in vitro reveals distinct patterns of innate immune evasion and activation” [J Hepatol (2023) 645–656]
Authors: Ombretta Colasanti, Rani Burm, Hao-En Huang, Tobias Riedl, Jannik Traut, Nadine Gillich, Teng-Feng Li, Laura Corneillie, Suzanne Faure-Dupuy, Oliver Grünvogel, Danijela Heide, Ji-Young Lee, Cong Si Tran, Uta Merle, Maria Chironna, Florian F.W. Vondran, Katharina Esser-Nobis, Marco Binder, Ralf Bartenschlager, Mathias Heikenwälder, Philip Meuleman, Volker Lohmann
Journal: Journal of Hepatology (2023)

Comparison of HAV and HCV infections in vivo and in vitro reveals distinct patterns of innate immune evasion and activationJournal of HepatologyVol. 79Issue 3PreviewHepatitis A virus (HAV) infections are considered not to trigger innate immunity in vivo, in contrast to hepatitis C virus (HCV). This lack of induction has been imputed to strong interference by HAV proteases 3CD and 3ABC. We aimed to elucidate the mechanisms of immune activation and counteraction by HAV and HCV in vivo and in vitro. Full-Text PDF Open Access It has come to our attention that there was an error in Fig. 4G (left panel) of our manuscript. The size of the protein Flag-3ABC was incorrectly labelled as '75 kDa' instead of its correct size '38 kDa'. This is corrected in the updated figure below. We apologise for any inconvenience caused.
Reply to Neder, to Ogata <i>et al.</i>, and to Graham
Authors: Surya P. Bhatt, Arie Nakhmani, Spyridon Fortis, Matthew J. Strand, Edwin K. Silverman, Frank C. Sciurba, Sandeep Bodduluri
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to Neder, to Ogata et al., and to Graham." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Use FEV<sub>1</sub>/FVC <i>Z</i>-Score Staging to Minimize Sex and Age Bias in Staging Chronic Obstructive Pulmonary Disease
Authors: Brian L. Graham
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Use FEV1/FVC Z-Score Staging to Minimize Sex and Age Bias in Staging Chronic Obstructive Pulmonary Disease." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Novel FEV<sub>1</sub>/FVC-based Diagnosis and Severity Classification of Chronic Obstructive Pulmonary Disease: How about FEV<sub>1</sub> % Predicted Basing?
Authors: Hiroaki Ogata, Yasuyoshi Washio, Makoto Yoshida
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Novel FEV1/FVC-based Diagnosis and Severity Classification of Chronic Obstructive Pulmonary Disease: How About FEV1 Percent Predicted Basing?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.